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A Novel Gene Crispld2 may Contribute to Facial Dysmophology in a Chicken Model of Crouzon's Syndrome
Author(s) -
Li Xin,
Tropp Stephen,
Young Nathan,
Hallgrimsson Benedikt,
Marcucio Ralph
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.907.15
Subject(s) - craniosynostosis , craniofacial , biology , mesenchyme , craniofacial abnormality , gene , embryo , genetics
Craniosynostosis causes malformations of the skull that are characterized by premature suture closure, as well as malformations of the brain and face. Recent work in mice, and our data, suggest that the malformations in the brain and face are a primary consequence of mutations that produce craniosynostosis. Mutations in FgfR1–3 account for ~25% of craniosynostosis syndromes. To investigate mechanisms underlying these facial malformations, we infected chick embryos with a retrovirus encoding FgfR2C278F. Compared to controls, treated embryos have widened‐faces and midfacial dysplasia resembling defects seen in craniosynostosis. Further, microarray analysis detected changes in gene expression. In particular, Crispld2 (cysteine rich secretory LCCL domain protein 2), a nonsyndromic cleft lip/palate related gene, is downregulated. The function of Crispld2, and how it may contribute to cleft lip, is unknown. We detected Crispld2 expression in facial mesenchyme in chicken embryos at HH 22. To assess function of this gene, we created an RCAS vector encoding Crispld2. Infected chicken fibroblasts appeared to migrate faster than controls cells, but embryos infected with the virus appeared normal. Therefore, we are currently investigating the effect of knocking‐down Crispld2. In conclusion, we have identified a novel gene Crispld2 and are determining the role this gene plays in craniofacial development. Grant Funding Source : NIH